Frontiers in Neuroscience,
Journal Year:
2024,
Volume and Issue:
18
Published: Oct. 29, 2024
Background
Auditory
verbal
hallucinations
(AVHs)
are
one
of
the
signature
positive
symptoms
schizophrenia,
affecting
a
substantial
portion
patients
with
schizophrenia.
These
seriously
impact
lives
patients,
resulting
in
social
burden.
Recent
studies
have
shown
significant
correlation
between
abnormal
local
brain
activity
and
neurobiological
mechanisms
AVHs.
However,
it
is
not
fully
clear
whether
altered
intrinsic
schizophrenia
AVHs
correlated
specific
neurotransmitter
systems.
Methods
We
included
50
first-episode,
drug-naïve
AVHs,
without
(NAVHs),
age-
sex-matched
healthy
controls
(HCs).
The
amplitude
low-frequency
fluctuation
(ALFF)
was
utilized
to
explore
AVH
group.
Subsequently,
we
spatially
ALFF
maps
using
JuSpace.
Results
In
our
study,
compared
HCs,
group
exhibited
significantly
reduced
multiple
regions,
mainly
including
left
precuneus,
bilateral
supplementary
motor
areas,
paracentral
lobules,
precentral
gyri,
postcentral
gyri.
NAVH
showed
inferior
occipital
gyrus,
calcarine
lingual
gyrus
HCs.
Furthermore,
higher
right
frontal
Additionally,
these
alterations
were
closely
related
three
neurotransmitters,
dopamine,
serotonin
norepinephrine.
Conclusion
link
neurotransmitters
contributing
comprehensive
understanding
pathophysiological
processes
treatment
pathways
underlying
Neurobiology of Disease,
Journal Year:
2023,
Volume and Issue:
185, P. 106254 - 106254
Published: Aug. 7, 2023
Presently,
neurotransmitter
deficits
in
GBA-related
Parkinson's
disease
(GBA-PD)
and
relationships
with
cognitive
impairment
are
poorly
understood.
A
better
understanding
of
impairments
GBA-PD
-
particularly
the
newly
diagnosed
drug-naïve
phase
may
support
developing
targeted
intervention
strategies.
We
aimed
to
investigate
patterns
idiopathic
PD
(iPD)
performance
correlations.We
recruited
189
patients
for
GBA
sequencing.
Voxel-wise
gray
matter
volume
(GMV)
was
evaluated
a
subgroup
17
GBA-PD,
100
iPD,
32
age-
sex-matched
healthy
controls
(HCs).
The
JuSpace
toolbox
covering
various
maps
helped
assess
whether
spatial
GMV
alterations
or
iPD
(relative
HCs)
were
associated
specific
systems.GBA-PD
indicated
widespread
GM
atrophy
fronto-temporal-occipital
region
compared
HCs.
spatially
correlated
serotonergic,
dopaminergic,
acetylcholinergic
pathway
distributions
(p
<
0.05,
false
discovery
rate
corrected).
Executive
function
language
domains
also
strength
colocalization
circuits.Regional
related
de
novo
could
provide
new
insights
into
pathophysiological
processes,
facilitating
potential
therapeutic
targets
management.
Nature Communications,
Journal Year:
2023,
Volume and Issue:
14(1)
Published: Sept. 26, 2023
Abstract
Parkinson’s
disease
involves
multiple
neurotransmitter
systems
beyond
the
classical
dopaminergic
circuit,
but
their
influence
on
structural
and
functional
alterations
is
not
well
understood.
Here,
we
use
patient-specific
causal
brain
modeling
to
identify
latent
receptor-mediated
mechanisms
contributing
progression.
Combining
spatial
distribution
of
15
receptors
from
post-mortem
autoradiography
with
6
neuroimaging-derived
pathological
factors,
detect
a
diverse
set
influencing
gray
matter
atrophy,
activity
dysregulation,
microstructural
degeneration,
dendrite
transporter
loss.
Inter-individual
variability
in
receptor
correlates
symptom
severity
along
two
distinct
axes,
representing
motor
psychomotor
symptoms
large
GABAergic
glutamatergic
contributions,
cholinergically-dominant
visuospatial,
psychiatric
memory
dysfunction.
Our
work
demonstrates
that
architecture
helps
explain
multi-factorial
re-organization,
suggests
distinct,
co-existing
processes
underlie
disease.
Brain Sciences,
Journal Year:
2024,
Volume and Issue:
14(6), P. 610 - 610
Published: June 18, 2024
Alcohol
misuse
is
associated
with
altered
punishment
and
reward
processing.
Here,
we
investigated
neural
network
responses
to
the
molecular
profiles
of
connectivity
features
predicting
alcohol
use
severity
in
young
adults.
We
curated
Human
Connectome
Project
data
employed
connectome-based
predictive
modeling
(CPM)
examine
how
functional
(FC)
during
wins
losses
are
severity,
quantified
by
Semi-Structured
Assessment
for
Genetics
Alcoholism,
981
combined
CPM
findings
JuSpace
toolbox
characterize
severity.
The
connectomics
appeared
specific,
comprising
less
than
0.12%
all
features,
including
medial
frontal,
motor/sensory,
cerebellum/brainstem
networks
processing
fronto-parietal,
motor/sensory
Spatial
correlation
analyses
showed
that
these
were
predominantly
serotonergic
GABAa
signaling.
To
conclude,
a
distinct
pattern
predicted
adult
drinkers.
These
“neural
fingerprints”
elucidate
impacts
brain
provide
evidence
new
targets
future
intervention.
Molecular Neurodegeneration,
Journal Year:
2025,
Volume and Issue:
20(1)
Published: Feb. 7, 2025
Cortical
atrophy
is
a
common
manifestation
in
behavioral
variant
frontotemporal
degeneration
(bvFTD),
exhibiting
spatial
heterogeneity
across
various
genetic
subgroups,
which
may
be
driven
by
distinct
biological
mechanisms.
We
employed
an
integrative
imaging
transcriptomics
approach
to
identify
both
disparate
and
shared
transcriptomic
signatures
associated
with
cortical
thickness
bvFTD
C9orf72
repeat
expansions
or
pathogenic
variants
GRN
MAPT.
Functional
enrichment
analyses
were
conducted
on
each
gene
list
significantly
thickness.
Additionally,
we
mapped
neurotransmitter
receptor/transporter
density
maps
the
maps,
uncover
different
correlation
patterns
for
form.
Furthermore,
examined
whether
identified
genes
enriched
pathology-related
using
previously
linked
TDP-43
positive
neurons
tau
pathology.
For
form
of
bvFTD,
sets
them.
The
GRN-bvFTD
involved
system
circadian
entrainment.
correlations
between
synaptic
thinning,
further
confirmed
critical
role
neurotransmission
signaling
shaping
brain
structure,
especially
group.
observed
significant
overlap
pathology
C9orf72-bvFTD
but
not
MAPT-bvFTD
group
providing
specificity
our
associations.
also
displaying
consistent
directionality,
those
either
negative
showing
same
direction
(positive
negative)
GRN-bvFTD.
displayed
more
pronounced
differences
compared
other
two
forms.
that
exhibited
showed
opposing
directionality
Overall,
this
several
new
regional
vulnerability
increased
interpretation
including
pathologically-specific
expression.
These
findings
illuminated
intricate
molecular
underpinnings
contributing
heterogeneous
nature
disease
distribution
backgrounds.
Neurobiology of Disease,
Journal Year:
2025,
Volume and Issue:
unknown, P. 106897 - 106897
Published: April 1, 2025
Neurodegenerative
diseases,
including
Alzheimer's
disease
(AD),
mild
cognitive
impairment
(MCI),
and
frontotemporal
dementia
(FTD),
are
a
growing
public
health
challenge,
with
incidence
projected
to
triple
in
the
coming
decades.
AD
is
associated
memory
impairment,
bvFTD
behavioral
dysfunction,
MCI
as
transitional
stage
between
normal
cognition
dementia.
While
structural
brain
changes
have
been
widely
studied,
role
of
neurotransmitter
pathways
remains
underexplored.
This
study
aims
correlate
gray
matter
atrophy
AD,
bvFTD,
identify
distinctive
neurochemical
impairments.
We
included
214
participants
(89
CE,
74
51
MCI)
from
single-center
cohort.
MRI
3
T
scanners
was
segmented
via
FreeSurfer.
Neurotransmitter
maps
were
sourced
JuSpace.
performed
volumetric
whole-brain
correlation
analyses
evaluate
relationships
regional
volumes
(BRVs)
pathways.
Group
differences
assessed
Kruskal-Wallis
tests
followed
by
post-hoc
analyses.
Volumetric
analysis
showed
expected
patterns
each
group.
Correlation
indicated
distinct
involvement:
significant
correlations
dopamine
D2
GABA
A
receptor
distribution;
had
negative
mu-opioid
receptor;
exhibited
early
serotonergic
dysregulation.
identified
linked
specific
systems,
showing
unique
profiles.
In
precuneus
inferior
parietal
lobules
aligns
dopaminergic
GABAergic
receptors,
potentially
impacting
executive
functions.
medial
orbitofrontal
temporal
atrophy,
possibly
contributing
symptoms.
MCI,
dysregulation
involving
SERT
occurs
before
detectable
atrophy.
Translational Neurodegeneration,
Journal Year:
2025,
Volume and Issue:
14(1)
Published: April 16, 2025
Abstract
Heterozygous
mutations
in
GRN
gene
lead
to
insufficient
levels
of
the
progranulin
(PGRN)
protein,
resulting
frontotemporal
dementia
(FTD)
with
TAR
DNA-binding
protein
43
(TDP-43)
inclusions,
classified
pathologically
as
lobar
degeneration
(FTLD-TDP).
Homozygous
are
exceedingly
rare
and
cause
neuronal
ceroid
lipofuscinosis
11,
a
lysosomal
storage
disease
onset
young
adulthood,
or
an
FTD
syndrome
late-onset
manifestations.
In
this
review,
we
highlight
broad
spectrum
clinical
phenotypes
associated
PGRN
deficiency,
including
primary
progressive
aphasia
behavioral
variant
dementia.
We
explore
these
alongside
relevant
rodent
vitro
human
models,
ranging
from
induced
pluripotent
stem
cell-derived
neural
progenitors,
neurons,
microglia,
astrocytes
genetically
engineered
heterotypic
organoids
containing
both
neurons
astrocytes.
summarize
advantages
limitations
models
recapitulating
main
FTLD-
hallmarks,
highlighting
role
non-cell-autonomous
mechanisms
formation
TDP-43
pathology,
neuroinflammation,
neurodegeneration.
Data
obtained
patients’
brain
tissues
biofluids,
parallel
single-cell
transcriptomics,
demonstrate
complexity
interactions
among
highly
heterogeneous
cellular
clusters
present
brain,
astrocytes,
oligodendroglia,
endothelial
cells,
pericytes.
Emerging
evidence
has
revealed
that
deficiency
is
cell
cluster-specific,
often
conserved,
genetic
molecular
central
nervous
system.
focus
on
how
distinct
populations
their
dysfunctional
crosstalk
contribute
neurodegeneration
neuroinflammation
FTD-
.
Specifically,
characterize
lipid
droplet-accumulating
microglia
alterations
myelin
content
dysfunction
caused
by
deficiency.
Additionally,
consider
deregulation
glia-neuron
communication
affects
exchange
organelles
such
mitochondria,
removal
excess
toxic
products
aggregates,
PGRN-related